Activation and repression of mammalian gene expression by the c-myc protein.-猫眼课题宝

c-myc 蛋白对哺乳动物基因表达的激活和抑制。

DOI：

10.1101/gad.1.4.347

发表时间：

1987

期刊：

Genes & development

影响因子：

10.5

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

R. Kaddurah;J. Greene;A. Baldwin;R. Kingston

核定位癌基因可能转化细胞的一种机制是通过调节基因表达的能力。我们表明，c-myc蛋白刺激人类热休克蛋白70(HSP70)启动子适当启动的表达水平。完全激活所需的序列位于转录起始点的上游，与基础表达所需的序列不同。这些序列似乎也不同于热诱导、血清诱导和乳头状病毒T抗原诱导所必需的启动子序列。C-myc蛋白抑制由小鼠金属硫蛋白I(MT-I)启动子启动的适当表达。去除外显子2的138个氨基酸的突变会产生一种c-myc基因产物，该产物能够激活HSP70启动子，但不再能够抑制MT-I的表达，这表明这两种特性位于c-myc蛋白的不同区域。腺病毒EII启动子的表达受到轻微抑制，而SV40早期启动子的表达受c-myc蛋白的影响最小。受c-myc蛋白调控的启动子的谱和该调控的序列要求都不同于以前描述的病毒反式激活蛋白。这些数据表明，c-myc蛋白可以以一种新的方式刺激和抑制哺乳动物启动子的转录。

One mechanism by which nuclear-localized oncogenes might transform cells is through an ability to regulate gene expression. We show that the c-myc protein stimulates the level of appropriately initiated expression from the human heat shock protein 70 (hsp70) promoter. Sequences required for full activation lie upstream of the transcription initiation site and are distinct from sequences necessary for basal expression. These sequences also appear distinct from promoter sequences necessary for heat induction, serum induction, and induction by the papovavirus T antigens. The c-myc protein inhibits appropriately initiated expression from the mouse metallothionein I (MT-I) promoter. A mutation that removes 138 amino acids of exon 2 produces a c-myc gene product that is capable of activating the hsp70 promoter but is no longer capable of inhibiting MT-I expression, suggesting that these two properties reside in different domains of the c-myc protein. Expression from the adenovirus EII promoter is slightly inhibited, while expression from the SV40 early promoter is minimally affected by the c-myc protein. Both the spectrum of promoters regulated by the c-myc protein and the sequence requirements for that regulation differ from those of previously characterized viral trans-activating proteins. The data suggest that the c-myc protein can both stimulate and inhibit transcription from mammalian promoters in a novel manner.